Teratozoospermia and asthenozoospermia are associated with specific epigenetic signatures

Abstract

SUMMARYSemen analysis is commonly used as a tool to assess the fertility potential of a male, despite its relatively low predictive power. In this study, we have assessed associations between semen analysis findings (low count, low motility, low viability, poor sperm penetration assay results, poor morphology, and increased DNA damage) and DNA methylation patterns in mature spermatozoa. DNA methylation patterns in the mature spermatozoa are thought to be indicative of patterns in the adult germline stem cells and may offer insight into potential perturbations to cellular pathways involved in spermatogenesis. In this study, sperm DNA methylation at >480,000 CpGs was assessed in 94 men using the Illumina 450k HumanMethylation Array and compared to standard measures of sperm quality. We did not identify any global changes to methylation profiles that were associated with reduced semen parameters. Similarly, we found no significant difference in methylation variability that was associated with any abnormal semen analysis parameter, although sperm displaying abnormal parameters tended to have an increased coefficient of variability, suggesting that, in some samples, this may be a contributing factor. Analysis of methylation at single CpGs and genomic regions did identify associations for low viability and low motility, and to a smaller extent, low count. Interestingly, based on GO Term analysis, differentially methylated regions associated with low viability were over-represented in regions important in meiosis, spermatogenesis, and genomic imprinting. These results suggest that while there are not global alterations to the sperm methylome associated with semen abnormalites, some viability associated regional alterations do exist that may be indicative of perturbed cellular pathways during spermatogenesis.

Cigarette smoking significantly alters sperm DNA methylation patterns

“…Following this lysis step, a visual check was performed under 400× magnification to confirm the absence of somatic cells, then sperm DNA was isolated using a sperm specific modification commonly used in our lab to a column-based extraction protocol using the DNeasy DNA isolation kit (Qiagen, Valencia CA)(Jenkins et al, 2013; Jenkins et al, 2014a). In addition to the visual check, a post hoc analysis of methylation data at the DLK1 locus, a region that is unmethylated in sperm and fully methylated in leukocytes, was evaluated to further confirm a pure sperm population as detailed previously (Jenkins et al, 2016). …”

Spermatozoa from males with reduced fecundity exhibit differential DNA methylation patterns

“…In recent decades, many studies have found that approximately 60% of infertility cases are classified as unexplained infertility (Erenpreiss et al, 2006;Anawalt, 2013;Yassin et al, 2017). Besides genetic causes, aberrant patterns of DNA methylation and histone modification have been shown to play a role in male infertility or fecundity decline, and have been identified in 15-30% of infertile males (Amor & Halliday, 2008;Pliushch et al, 2010;Esteves, 2013;Soubry, 2015;Jenkins et al, 2016a). The molecular mechanisms of these defects need more clarification and explanation since male infertility has been clarified as a phenotype of the deficiency in the transcription of various single genes (Matzuk & Lamb, 2002).…”

Treatment of idiopathic oligozoospermia with combined human chorionic gonadotropin/human menopausal gonadotrophin: A randomised, double‐blinded, placebo‐controlled clinical study

“…According to the guideline of WHO, , semen was collected into sterilised glass containers by masturbation after a 3–5 day abstinence. After evaluation of liquefaction and measurement of viscosity and volume, motility was measured at room temperature (22–25°C), 1 hr after ejaculation as previously described (Auger, Jouannet, & Eustache, ; Ben Khelifa et al, ; Jenkins et al, ; Rowe, Comhaire, Hargreave, & Mahmoud, ; WHO, ). Sperm concentration was calculated in an undiluted semen specimen using Makler ' s Counting Chamber (Makler, ; Panidis et al, ).…”